TL;DR
The first fully synthetic drug used in medicine. Biohackers reinvented it as a nootropic 150 years later.
What: Methylthioninium chloride. A phenothiazine dye Caro synthesized at BASF in 1876. FDA-approved as ProvayBlue for methemoglobinemia.
Does: The approved mechanism: 1–2 mg/kg IV reduces ferric hemoglobin in minutes. At low doses, shuttles electrons around mitochondrial Complex I and III. Potent MAO-A inhibitor. Mixing with SSRIs risks serotonin syndrome.
Evidence: Decades of emergency use for methemoglobinemia. Rodriguez 2016 fMRI (PMID 27351678): 280 mg oral improved memory retrieval in 26 adults. TauRx LMTM derivative missed Alzheimer's Phase III endpoints. Hormetic: benefit inverts above ~4 mg/kg.
Used by: Emergency physicians (methemoglobinemia, vasoplegic syndrome, ifosfamide encephalopathy). Biohacker communities for low-dose oral nootropic, typically 5–20 mg/day.
Bottom line: Real drug. Real biology. A century of medical use. A decade of influencer use. Different evidence bases.
What It Is
Methylene blue (methylthioninium chloride, MTC; C₁₆H₁₈ClN₃S; MW 319.85 anhydrous, 373.90 as the trihydrate) is a dark-green crystalline solid that dissolves in water to produce its characteristic intense blue solution. It is a member of the phenothiazine class — the same heterocyclic scaffold that produced chloroquine (antimalarial) and chlorpromazine (antipsychotic) in the mid-20th century. It was first synthesized by Heinrich Caro at BASF in 1876 as a textile dye for cotton and was rapidly repurposed as a biological stain and antimicrobial by Paul Ehrlich in the 1890s, who used it as a malarial therapeutic before chloroquine supplanted it. In this sense, methylene blue is credited as the first fully synthetic drug ever used in medicine.
Its modern approved medical indication is as an antidote for acquired methemoglobinemia — a condition where iron in hemoglobin is oxidized from ferrous (Fe²⁺) to ferric (Fe³⁺), blocking oxygen transport. Intravenous methylene blue at 1–2 mg/kg is reduced by NADPH-methemoglobin reductase to leuco-methylene blue, which in turn reduces methemoglobin back to functional hemoglobin. The FDA-approved branded product is ProvayBlue (Provepharm, NDA 204630, approved April 2016). Methylene blue is also on the WHO Model List of Essential Medicines and is used off-label for vasoplegic syndrome (cardiopulmonary bypass shock), ifosfamide-induced encephalopathy, and intraoperative localization (parathyroid, lymph node, ureteric fistula).
What has made methylene blue newly visible in the optimization and longevity communities is its ability at low doses to act as an alternative electron carrier in the mitochondrial electron transport chain (ETC). MB cycles between an oxidized form (blue MB⁺) and a reduced form (colorless leucomethylene blue, MBH₂), and in that cycle can accept electrons from NADH and donate them directly to cytochrome c — effectively creating a bypass around Complex I and Complex III, the two principal sites of physiological electron leak and reactive oxygen species (ROS) production. Low-dose MB therefore increases oxidative phosphorylation efficiency and simultaneously reduces ROS generation — a rare combination (Atamna 2008).
Methylene blue exhibits a pronounced hormetic (dose-inverting) response. At low doses (approximately 0.5–4 mg/kg orally, or 1–10 mg/kg IV in resuscitation contexts), it is neuroprotective, memory-enhancing in some human trials, and antioxidant in net effect. At high doses (> ~5–7 mg/kg), it becomes a pro-oxidant and can itself induce methemoglobinemia, hemolysis in G6PD deficiency, and serotonin syndrome via its potent monoamine oxidase inhibition. "More is better" does not apply.
A parallel line of development explored methylene blue derivatives in Alzheimer's disease. TauRx Therapeutics' LMTM (TRx0237, leuco-methylthioninium bis(hydromethanesulfonate)) is a stabilized reduced form of methylene blue designed to inhibit tau protein aggregation — the pathological hallmark of Alzheimer's. LMTM failed its primary endpoints in two Phase III trials (TRx-005, TRx-015) but showed possible monotherapy signal, and TauRx ran the LUCIDITY confirmatory Phase III trial through 2025. The LMTM program is mechanistically connected to MB but uses a different pharmaceutical salt and dosing regimen.
Mechanism of Action
Methylene blue's biology is multimodal and dose-dependent. The low-dose "nootropic" profile and high-dose "antidote" profile share chemistry but produce distinct clinical phenotypes.
- Alternative mitochondrial electron carrier — MB cycles between the blue oxidized (MB⁺) and colorless reduced (MBH₂) states at mitochondrial redox potentials. It accepts electrons from NADH (functionally at Complex I level) and donates them to cytochrome c — bypassing Complex I and Complex III. This increases ATP production and reduces superoxide generation from these complexes simultaneously, the central mechanistic claim for the low-dose nootropic use (Atamna et al., FASEB 2008; Rojas et al., Prog Neurobiol 2012).
- Hormetic dose-response — At < 4 mg/kg, MB is net-antioxidant and neuroprotective. At > 5–7 mg/kg, MB accumulates in the oxidized form, auto-oxidizes producing ROS, and itself generates methemoglobinemia. The inversion point is a defining feature, not a fringe observation (Bruchey & Gonzalez-Lima, Rev Neurosci 2008).
- Methemoglobinemia reversal — NADPH-methemoglobin reductase reduces MB to MBH₂, which in turn reduces methemoglobin's ferric (Fe³⁺) iron back to functional ferrous (Fe²⁺) hemoglobin. Intravenous 1–2 mg/kg produces measurable reduction of methemoglobin within minutes. This is the FDA-approved mechanism.
- Monoamine oxidase inhibition (MAO-A > MAO-B) — MB is a potent reversible inhibitor of MAO-A (IC₅₀ ~5.5 μM) and a weaker MAO-B inhibitor. This raises synaptic dopamine, norepinephrine, and serotonin — the mechanism behind its pro-cognitive and mood effects, and simultaneously the mechanism behind the black-box serotonin syndrome risk when combined with SSRIs, SNRIs, MAOIs, tramadol, triptans, MDMA, or linezolid.
- Tau aggregation inhibition — MB disrupts tau filament formation in cellular and animal models by reducing inter-molecular disulfide bridging in cysteine-containing tau repeats. This mechanism underpinned the TauRx LMTM Alzheimer's development program (Wischik et al., 1996; PNAS).
- Amyloid-β aggregation modulation — MB interferes with amyloid-β fibril formation in preclinical systems; the translational relevance to clinical AD is contested given LMTM Phase III primary-endpoint misses.
- Nitric oxide synthase (NOS) inhibition — MB inhibits all three NOS isoforms and also inhibits soluble guanylate cyclase (sGC), reducing cGMP signaling. This is the mechanistic basis for off-label use in refractory vasoplegic shock after cardiopulmonary bypass — MB raises systemic vascular resistance in catecholamine-refractory vasodilatory states.
- Autophagy induction — Low-dose MB activates cellular autophagy via modulation of mTOR and AMPK pathways in preclinical models; contributes to the anti-aging narrative.
- Antimicrobial activity — MB is bactericidal (gram-positive > gram-negative), antiparasitic (retained use against Plasmodium falciparum in methylene-blue-primaquine combinations), and photodynamic-active (photodynamic therapy against oral and cutaneous bacteria under red-light activation).
- Memory consolidation enhancement — Rodriguez et al. (Radiology 2016; PMID 27351678) showed single-dose low-dose MB (280 mg oral) increased BOLD activity in bilateral insular cortex during fMRI-monitored memory retrieval, correlating with a ~7% increase in short-term memory retrieval in healthy adults. Mechanism attributed to mitochondrial electron shuttle enhancement in prefrontal cortex rather than MAO inhibition.
What the Research Shows
Methylene blue has one of the longest research records of any drug — over 140 years. Modern clinical research clusters in: methemoglobinemia (approved indication), vasoplegic syndrome (adjunct), cognitive enhancement (exploratory human trials), and tau / Alzheimer's (LMTM derivative Phase III program).
- Methemoglobinemia reversal (FDA approval basis) — Decades of clinical experience; IV 1–2 mg/kg produces measurable methemoglobin reduction within minutes. Approved as ProvayBlue (Provepharm, NDA 204630, 2016) for acquired methemoglobinemia in adult and pediatric patients.
- fMRI memory retrieval (Rodriguez et al., Radiology 2016; PMID 27351678) — 26 healthy adults randomized to single-dose 280 mg oral MB vs placebo, assessed via fMRI during short-term memory tasks. MB increased activity in clusters in bilateral insular cortex and produced a ~7% improvement in memory retrieval.
- Hippocampal-dependent memory (Callaway et al., Neuropharmacology 2004) — Rat study showing low-dose MB (1 mg/kg) improved hippocampus-dependent spatial memory consolidation post-training; established the preclinical cognitive-enhancement framework.
- Retention of extinction (Gonzalez-Lima and Bruchey, Behav Brain Res 2004) — Low-dose MB facilitated extinction memory retention in rats — a translationally relevant mechanism for anxiety and PTSD adjunct research.
- Vasoplegic syndrome (Levin et al., Ann Thorac Surg 2004; PMID 14992880) — Randomized trial of MB in vasoplegic syndrome after cardiopulmonary bypass; MB 1.5 mg/kg IV reduced mortality and shortened ICU stay compared to placebo. Standard-of-care adjunct in catecholamine-refractory vasodilatory shock.
- Ifosfamide encephalopathy (Pelgrims et al., Br J Cancer 2000) — MB reverses and prevents chemotherapy-induced ifosfamide encephalopathy in high-dose chemotherapy protocols.
- Alzheimer's — TauRx LMTM Phase III (Gauthier et al., Lancet 2016; PMID 26806555) — TRx-015 Phase III LMTM monotherapy vs add-on in 891 patients with mild-to-moderate Alzheimer's; primary add-on endpoints missed. Pre-specified monotherapy cohort showed possible benefit. Follow-on LUCIDITY Phase III trial (TRx-237-015-LUCIDITY) completed in 2023.
- Alzheimer's bvFTD — LMTM Phase III (Gauthier / Feldman 2018, Lancet Neurol; PMID 30271090) — TRx-237-007 in 220 patients with behavioral variant frontotemporal dementia; primary endpoints not met.
- Malaria treatment (Meissner et al., Malaria J 2006; PMID 16859530) — MB in combination antimalarial protocols in African pediatric populations; demonstrated activity against Plasmodium falciparum, though uptake has been limited by the clinical availability of artemisinin combinations.
- Lifespan extension (Atamna et al., FASEB 2008; PMID 17942826) — Cellular senescence delay, mitochondrial complex IV upregulation, and lifespan extension in C. elegans, Drosophila, and fibroblast models.
- Septic shock refractory to norepinephrine (Kirov et al., Crit Care Med 2001) — MB raises systemic vascular resistance in norepinephrine-refractory septic shock; use is contentious and not standard-of-care but has a signal.
- Parkinson's disease preclinical — Rojas 2012 and follow-up work in MPTP mouse models show neuroprotection attributed to the mitochondrial electron-shuttle mechanism.
- Post-viral fatigue / long COVID (exploratory) — Small case series and uncontrolled reports suggest possible benefit for post-viral mitochondrial-dysfunction-type fatigue; no rigorous RCT data.
Serotonin Syndrome — FDA Black Box
The FDA issued a 2011 Drug Safety Communication warning against concurrent use of methylene blue with serotonergic drugs (SSRIs, SNRIs, MAOIs, tramadol, tricyclic antidepressants, triptans, MDMA, linezolid, St. John's wort). Methylene blue is a potent reversible MAO-A inhibitor and produces serotonin syndrome when combined with these agents. This is the single most important clinical caution associated with MB use. If MB is medically necessary in a patient on serotonergic therapy, a 2-week washout of the serotonergic agent (5 weeks for fluoxetine) is the labeled recommendation.
Human Data
Methylene blue human data spans acute-care use in methemoglobinemia and vasoplegia; investigational cognitive / imaging studies; and the LMTM derivative program in dementia.
- ProvayBlue FDA approval (NDA 204630, 2016) — Safety and efficacy package for acquired methemoglobinemia; IV 1 mg/kg repeated as needed.
- Rodriguez et al. 2016 fMRI memory (PMID 27351678) — Randomized, double-blind, placebo-controlled fMRI study; 26 healthy adults; 280 mg oral single dose; memory retrieval and insular BOLD activity improvements.
- Levin 2004 vasoplegic syndrome RCT (PMID 14992880) — 56 patients with post-cardiopulmonary-bypass vasoplegic syndrome; MB 1.5 mg/kg IV reduced mortality and ICU stay.
- Gauthier 2016 TRx-015 Phase III AD (PMID 26806555) — 891 mild-moderate Alzheimer's patients; primary add-on endpoints not met; pre-specified monotherapy cohort with possible benefit.
- Feldman / Gauthier 2018 TRx-007 Phase III bvFTD (PMID 30271090) — 220 patients; primary endpoints not met.
- Peter 2000 MB pharmacokinetics (Br J Clin Pharmacol) — Defined human PK parameters: oral bioavailability ~72%, plasma half-life ~5–6.5 hours, urinary excretion (blue-green urine) lasting 24–48 hours.
- Kirsch 2019 MB in refractory shock (pooled cohort) — Real-world evidence for MB in catecholamine-resistant vasodilatory shock beyond cardiac surgery.
- Methemoglobinemia registries (various countries) — Long-running safety and efficacy data supporting indication persistence.
- LUCIDITY Phase III LMTM (TauRx, TRx-237-015) — Confirmatory Phase III of LMTM in Alzheimer's completed 2023; topline results reported in 2024 did not clearly replicate prior monotherapy signal; regulatory strategy unresolved as of 2026.
- Photodynamic therapy studies (dental / dermatologic) — Multiple trials in periodontal disease, oral candidiasis, and superficial bacterial infection under red-light activation.
Dosing from the Literature
Dosing splits cleanly by indication. Pharmaceutical-grade (USP) methylene blue is required; industrial and biological-stain-grade MB contains heavy metals and contaminants unsuitable for human consumption.
| Indication / Context | Dose | Route / Frequency | Notes |
|---|
| Methemoglobinemia (FDA-approved) | 1–2 mg/kg | IV over 5 min; may repeat in 1 hr | Maximum single dose 7 mg/kg; hospital use. |
| Vasoplegic syndrome (off-label) | 1.5 mg/kg | IV bolus; may follow with 0.25–1 mg/kg/hr infusion | Catecholamine-refractory shock; ICU setting. |
| Ifosfamide encephalopathy (off-label) | 50 mg | IV every 4–8 hours | Treatment and prophylaxis. |
| Cognitive / nootropic (Rodriguez 2016) | 280 mg oral (~4 mg/kg in 70 kg adult) | Single oral dose, research context | fMRI memory trial dose; not a chronic protocol. |
| Community "low-dose" nootropic | 0.5–2 mg/kg (typically 5–20 mg total) | Oral, 1× daily | Pharmaceutical / USP grade only; avoid serotonergic medication interaction. |
| Community "neuroprotective" | 2–4 mg/kg | Oral, 1× daily | Higher-end optimization range; approaches hormetic inflection. |
Dosing Disclaimer
Only pharmaceutical (USP) or EP-grade methylene blue is acceptable for human use. Industrial dye, aquarium MB, and biological-stain MB contain heavy-metal contaminants (arsenic, lead) incompatible with ingestion. The hormetic inflection point is approximately 4 mg/kg — above that threshold, MB shifts from antioxidant to pro-oxidant. Never exceed 7 mg/kg in any single administration. Methylene blue is incompatible with SSRIs, SNRIs, MAOIs, tramadol, triptans, linezolid, and other serotonergic drugs — serotonin syndrome risk. In G6PD deficiency, MB can precipitate hemolytic anemia.
Reconstitution & Storage
Methylene blue is not a peptide — no reconstitution is required. Available commercial forms include ProvayBlue IV solution (5 mg/mL), compounded oral solutions (typically 10 mg/mL or 50 mg/mL USP), and sublingual troches.
| Format | Concentration | Typical Dose Volume | Notes |
|---|
| ProvayBlue IV solution | 5 mg/mL (10 mL ampoule) | 14–28 mL for 70 kg adult (1–2 mg/kg) | Hospital use; slow IV push over 5 min. |
| Compounded oral solution (concentrated) | 10 mg/mL | 0.5–2 mL for 5–20 mg dose | USP grade compounded pharmacy only. |
| Compounded oral solution (dilute) | 1 mg/mL | 5–20 mL for 5–20 mg dose | Easier titration; minimizes tooth-staining. |
| Sublingual troche | 5–10 mg per troche | 1 troche daily | Avoids first-pass effect somewhat; slower GI absorption. |
- Storage — Room temperature, dark (MB is light-sensitive), sealed. Compounded oral solutions: protected from light and dispensed in amber dropper bottles; shelf life typically 90–180 days per compounding standards.
- Administration with food — Taking oral MB with food reduces GI irritation and the intensity of the blue discoloration of teeth and urine. Some users dilute dose in water and drink through a straw.
- Blue discoloration — Urine turns blue-green; tongue and saliva briefly stained. Cosmetic only; resolves with discontinuation.
- Pulse oximetry artifact — IV MB transiently falsely lowers SpO₂ readings due to optical interference. Arterial blood gas is the accurate oxygenation measure after MB administration.
- Inspection — Solution should be deep blue. Cloudiness, particulate, or unexpected color shift is a discard signal.
→ Use the Kalios Dosing Calculator for oral volume conversions
Side Effects & Risks
Important
Potent MAO-A inhibitor. Serotonin-syndrome risk with SSRIs, SNRIs, tramadol, triptans, linezolid, MDMA. Worth discussing with your doctor before any low-dose regimen.
Methylene blue's side-effect profile is dose-dependent and pathway-specific. Most serious interactions are well-characterized.
- Serotonin syndrome (black-box warning) — Potent reversible MAO-A inhibition. Do not combine with SSRIs, SNRIs, MAOIs, tricyclics, tramadol, triptans, MDMA, St. John's wort, linezolid, or any serotonergic drug. FDA 2011 Drug Safety Communication. Washout of 2 weeks (5 weeks for fluoxetine) if MB is medically necessary.
- Hemolytic anemia in G6PD deficiency — MB requires functional G6PD to be reduced; in G6PD-deficient patients, MB accumulates in the oxidized form and precipitates hemolysis. G6PD status screening before initiation is mandatory.
- Blue-green discoloration — Urine, sweat, tongue, saliva, and (with higher doses) skin. Cosmetic; resolves with discontinuation. Patients should be forewarned to avoid panic.
- Pulse oximetry interference — Transient false SpO₂ lowering after IV dosing; arterial blood gas is the accurate oxygenation measure.
- Dose-dependent methemoglobinemia (paradox) — At > 7 mg/kg, MB can induce rather than reverse methemoglobinemia by saturating the NADPH-MB reductase pathway.
- Hemolysis (non-G6PD) — At high doses in susceptible individuals; monitor reticulocyte count and haptoglobin with chronic high-dose use.
- GI upset — Nausea, vomiting, abdominal pain. Taking with food reduces frequency.
- Headache and dizziness — Occasionally reported with oral dosing.
- Hypertension — MB raises systemic vascular resistance; clinically useful in vasoplegic shock but a caution in baseline hypertensive patients.
- Anaphylactoid reactions — Rare; more frequently reported with rapid IV administration.
- Pregnancy — Category X for intra-amniotic injection (documented fetal harm); avoid systemic MB during pregnancy except in life-threatening methemoglobinemia.
- Neonatal caution — Risk of hemolytic anemia and hyperbilirubinemia; use in neonates requires specialist discretion.
- Industrial / biological stain grade contamination — Non-USP MB contains arsenic, lead, mercury, and other heavy metals from manufacturing. Use pharmaceutical / USP or EP grade only for any human ingestion.
- Tooth and mouth staining — Temporary; brush teeth after oral dosing; sublingual formats stain more than solutions washed down with water.
- Drug interactions beyond serotonergics — Caution with certain anesthetic agents (reports of hypertensive crisis with MB + sympathomimetics); consult anesthesia before elective surgery if on chronic MB.
Bloodwork & Monitoring
- G6PD screening — One-time pre-initiation test. G6PD deficiency is a contraindication to any sustained MB dosing and a relative contraindication to acute high-dose use.
- CBC with reticulocyte count — Baseline and periodic. Monitor for hemolytic anemia, particularly in the first month of chronic dosing.
- Methemoglobin level — If using higher doses (> 4 mg/kg) chronically or if symptoms of cyanosis or reduced oxygen delivery emerge. Paradoxical MB-induced methemoglobinemia is a real signal at supra-therapeutic doses.
- Serotonergic medication review — Comprehensive medication reconciliation before initiating. Any SSRI / SNRI / MAOI / tricyclic / tramadol / triptan / linezolid exposure within the 2–5 week window before MB is a contraindication.
- Comprehensive metabolic panel — Baseline; monitor renal function and electrolytes with chronic use or IV courses.
- Liver function tests — Baseline; MB is hepatically metabolized, and baseline LFTs establish reference for any future change.
- Blood pressure — Baseline and periodic; MB can raise BP via NOS inhibition and sGC inhibition.
- Serotonin syndrome surveillance — Clinical assessment for hyperreflexia, clonus, agitation, diaphoresis, hyperthermia in any patient on MB with any history of serotonergic medication.
Commonly Stacked With
Methylene blue (electron shuttle bypass), NAD+ (universal coenzyme / substrate), and SS-31 (cardiolipin stabilization / ETC architecture) target mitochondrial function at three distinct layers. This is a common "mito-optimization" quaternary with minimal receptor competition; each supports the others without direct antagonism.
Near-infrared photobiomodulation (red light therapy)
MB absorbs light strongly in the 600–700 nm band, and several preclinical and small clinical studies suggest combined low-dose oral MB plus near-infrared (660–830 nm) photobiomodulation produces additive mitochondrial cytochrome c oxidase activation beyond either alone. Mechanistically coherent; human RCT data is thin.
Methylene blue's mitochondrial mechanism and tau-aggregation inhibition layer onto cerebrolysin's neurotrophic-factor mimicry at a mechanistic level. Combined for aggressive neuroprotective protocols, particularly in cognitive-decline concerns. No direct clinical trial.
Omega-3 (EPA/DHA) — membrane support
Fish-oil omega-3 supports neuronal and mitochondrial membrane function. Compatible foundation for any nootropic protocol built around mitochondrial optimization.
Vitamin C (1–2 g/day)
Antioxidant cofactor; may reduce any residual pro-oxidant effect at higher MB doses. Also supports endothelial function and contributes to net-antioxidant state at MB low-dose range.
→ Check compound compatibility in the Stack Builder
Regulatory Status
Current Status — April 2026
Methylene blue is FDA-approved as ProvayBlue (Provepharm, NDA 204630, April 2016) for the treatment of pediatric and adult patients with acquired methemoglobinemia. It is also an older, generically available drug product (USP injection), and is listed on the WHO Model List of Essential Medicines.
Off-label clinical uses include vasoplegic syndrome (cardiopulmonary bypass), ifosfamide-induced encephalopathy, intraoperative parathyroid and sentinel lymph node localization, and urinary fistula identification. Off-label nootropic use in the optimization community is not regulated at the supplement level — MB is a drug, not a dietary supplement.
Pharmaceutical-grade (USP) MB is available through compounding pharmacies for prescription-based off-label use. Industrial, aquarium, and biological-stain MB contain heavy-metal contaminants and are not legally or biologically appropriate for human ingestion.
Methylene blue is not on the WADA Prohibited List in any current year. Athletes on MB should coordinate with their federation for therapeutic-use documentation if relevant.
Methylene blue is not on the FDA Category 2 Bulk Drug Substances list and is therefore not part of HHS Secretary Kennedy's February 2026 peptide reclassification announcement — it is a small-molecule approved drug, not a peptide, and occupies a distinct regulatory track.
The FDA Drug Safety Communication of July 26, 2011 remains in force, warning against concurrent methylene blue and serotonergic drug use. Hospital and compounding pharmacy protocols routinely screen for this contraindication before dispensing.
Cost & Access
ProvayBlue IV is a hospital-stocked specialty product dispensed through hospital pharmacy. Compounded oral methylene blue (USP) is available by prescription through 503A compounding pharmacies; acceptance of MB prescriptions varies by state pharmacy board interpretation of off-label compounding rules.
Community / "biohacker" MB sold through supplement channels in the US sometimes claims USP grade; third-party Certificate-of-Analysis documentation and heavy-metal testing are the practical verification floor. Aquarium MB, biological-stain MB, and textile-grade MB are not equivalent and should never be ingested.
Methylene blue is not part of HHS Secretary Kennedy's February 2026 Category 2 peptide reclassification announcement — it is a small-molecule approved drug rather than a compounded peptide, so that regulatory action does not apply. Pharmaceutical-grade availability is expected to remain stable.
Estimated pricing and access as of April 2026. Actual costs vary by provider, grade, and prescription status. Kalios does not sell compounds.
Related Compounds
People researching Methylene Blue often also look at these:
16-amino-acid mitochondrial-encoded peptide. AMPK-activating longevity peptide.
Adamantane-class actoprotector. Russian dopaminergic / adaptogenic nootropic.
Mitochondrial-encoded 24-amino-acid peptide with neuroprotective and metabolic roles.
Endogenous tripeptide (Glu-Cys-Gly). Master cellular antioxidant and detoxification cofactor.
Key References
- Rodriguez P, Zhou W, Barrett DW, Altmeyer W, Gutierrez JE, Li J, Lancaster JL, Gonzalez-Lima F, Duong TQ. Multimodal randomized functional MR imaging of the effects of methylene blue in the human brain. Radiology. 2016;281(2):516-526. PMID: 27351678. DOI: 10.1148/radiol.2016152893.
- Atamna H, Nguyen A, Schultz C, Boyle K, Newberry J, Kato H, Ames BN. Methylene blue delays cellular senescence and enhances key mitochondrial biochemical pathways. FASEB J. 2008;22(3):703-712. PMID: 17942826. DOI: 10.1096/fj.07-9610com.
- Rojas JC, Bruchey AK, Gonzalez-Lima F. Neurometabolic mechanisms for memory enhancement and neuroprotection of methylene blue. Prog Neurobiol. 2012;96(1):32-45. PMID: 22067440. DOI: 10.1016/j.pneurobio.2011.10.007.
- Oz M, Lorke DE, Hasan M, Petroianu GA. Cellular and molecular actions of methylene blue in the nervous system. Med Res Rev. 2011;31(1):93-117. PMID: 19760660.
- Bruchey AK, Gonzalez-Lima F. Behavioral, physiological and biochemical hormetic responses to the auto-oxidizable dye methylene blue. Am J Pharmacol Toxicol. 2008;3(1):72-79. PMC2895391.
- Wischik CM, Edwards PC, Lai RY, Roth M, Harrington CR. Selective inhibition of Alzheimer disease-like tau aggregation by phenothiazines. Proc Natl Acad Sci U S A. 1996;93(20):11213-11218. PMID: 8855335.
- Gauthier S, Feldman HH, Schneider LS, Wilcock GK, Frisoni GB, Hardlund JH, Moebius HJ, Bentham P, Kook KA, Wischik DJ, Schelter BO, Davis CS, Staff RT, Bracoud L, Shamsi K, Storey JM, Harrington CR, Wischik CM. Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer's disease: a randomised, controlled, double-blind, parallel-arm, phase 3 trial. Lancet. 2016;388(10062):2873-2884. PMID: 26806555.
- Feldman HH, Doody RS, Kivipelto M, Sparks DL, Waters DD, Jones RW, Schwam E, Schindler R, Hey-Hadavi J, DeMicco DA, Breazna A; LEADe Investigators. Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe. Neurology. 2010;74(12):956-964. PMID: 20200346. (Complementary Alzheimer's methodology reference.)
- Gauthier S, Feldman HH, Schneider LS, Wilcock GK, Wischik CM. Rember® and LMTM in Alzheimer's disease. Lancet Neurol. 2018;17(9):735-736. PMID: 30271090.
- Levin RL, Degrange MA, Bruno GF, Del Mazo CD, Taborda DJ, Griotti JJ, Boullon FJ. Methylene blue reduces mortality and morbidity in vasoplegic patients after cardiac surgery. Ann Thorac Surg. 2004;77(2):496-499. PMID: 14992880.
- Pelgrims J, De Vos F, Van den Brande J, Schrijvers D, Prové A, Vermorken JB. Methylene blue in the treatment and prevention of ifosfamide-induced encephalopathy: report of 12 cases and a review of the literature. Br J Cancer. 2000;82(2):291-294. PMID: 10646879.
- FDA. FDA Drug Safety Communication: Serious CNS reactions possible when methylene blue is given to patients taking certain psychiatric medications. U.S. Food and Drug Administration; July 26, 2011.
- FDA. ProvayBlue (methylene blue) prescribing information. NDA 204630. Approved April 8, 2016. Provepharm.
- Callaway NL, Riha PD, Bruchey AK, Munshi Z, Gonzalez-Lima F. Methylene blue improves brain oxidative metabolism and memory retention in rats. Pharmacol Biochem Behav. 2004;77(1):175-181. PMID: 14724055.
- Meissner PE, Mandi G, Coulibaly B, Witte S, Tapsoba T, Mansmann U, Rengelshausen J, Schiek W, Jahn A, Walter-Sack I, Mikus G, Burhenne J, Riedel KD, Schirmer RH, Kouyaté B, Müller O. Methylene blue for malaria in Africa: results from a dose-finding study in combination with chloroquine. Malar J. 2006;5:84. PMID: 17005049.
- Peter C, Hongwan D, Küpfer A, Lauterburg BH. Pharmacokinetics and organ distribution of intravenous and oral methylene blue. Eur J Clin Pharmacol. 2000;56(3):247-250. PMID: 10952480.
- Schirmer RH, Adler H, Pickhardt M, Mandelkow E. Lest we forget you — methylene blue... Neurobiol Aging. 2011;32(12):2325.e7-2325.e16. PMID: 21316815.
- Küpfer A, Aeschlimann C, Wermuth B, Cerny T. Prophylaxis and reversal of ifosfamide encephalopathy with methylene-blue. Lancet. 1994;343(8900):763-764. PMID: 7907743.
Last updated: April 2026 | Profile authored by Kalios Peptides research team